Monday, March 30, 2015

Sangamo Sublicensee Cellular Dynamics aquired this morning at 100% premium

Fujifilm will acquire CDI via an all-cash tender offer to be followed by a second step merger. Fujifilm aims to acquire all issued and outstanding shares of CDI's common stock for $ 16.5 per share or approximately $ 307 million (on a fully diluted basis). The offer represents a premium of 108% to CDI's closing price on March 27.

Cellular Dynamics has licensed patents covering  Sigma-Aldrich's CompoZr zinc finger nuclease technologies. The licensed technologies "facilitate efficient genomic editing by creating double-stranded breaks in DNA at user-specified locations, stimulating the cell's natural repair process and enabling targeted gene insertions, deletions, or modifications," CDI said in a statement.

Sigma-Aldrich licensed CompoZr ZFN technology from Sangamo and Sangamo earns royalties from the sale and licensing of that product.

Saturday, March 28, 2015

New job postings at Sangamo

Things are moving rapidly; only 2 days between updates.

Job Opportunities

The following is a list of open positions with Sangamo BioSciences.
(Updated 03/27/15)

Journeyman.tv video "The First Man To Be Cured Of HIV"

My earlier post presented a video describing the scientific work of Paula Cannon of USC.
This video reviews the background leading the the discovery of the CCR5- mutation, Timothy Ray Brown, Sangamo Biosciences and again the work of Dr. Cannon.

https://www.youtube.com/watch?v=BgxQDJRUL5Q

Over $90,000 of SGMO traded after hours 3/27/2015

Here are the post 5pm eastern trades of SGMO after hours on Friday 3/27/2015:
total shares traded after 5pm est, 6335
18:59 $ 15.90 High 200
18:58 $ 15.90  200
 18:58 $ 15.90  500
 18:58 $ 15.90  2,500
 18:58 $ 15.90  100
 18:58 $ 15.90  2,300
 18:57 $ 15.90  200
 17:00 $ 15.21 Low 335

Read more: http://www.nasdaq.com/symbol/sgmo/after-hours#ixzz3Vh9qaIUc

Review of Sangamo HIV IND in Hematopoetic Stem Cells

In light of the recent acceptance of the City of Hope and Sangamo BioSciences IND treatment of HIV using hematopoetic stem cells announced on February 26th of this year I found it useful to review this youtube video. In 12 minutes Paula Cannon of USC explains the rational and hope for this soon to be opened study. Her presentation is titled "Can Gene Therapy cure HIV/AIDS?".

https://www.youtube.com/watch?v=plvv07vd5iI

Friday, March 27, 2015

Taiwaneese group using ZFNs to delete CCR5 in Mesenchymal stem cells

Generation of CCR5-defective CD34 cells from ZFN-driven stop codon-integrated mesenchymal stem cell clones

Krissanapong Manotham*, Supreecha Chattong and Anan Setpakdee
 

Abstract (provisional)

Backgrounds Homozygous 32-bp deletion of the chemokine receptor 5 gene (CCR5) is associated with resistance to human immunodeficiency virus (HIV) infection, while heterozygosity delays HIV progression. Bone marrow transplantation (BMT) from a 32/32 donor has been shown to cure an HIV-infected patient. However, the rarity of this mutation and the safety risks associated with current BMT protocols are the major obstacles to this treatment. Zinc finger nuclease (ZFN) targeting is a powerful method for achieving genomic disruption at specific DNA sites of interest. Results Taking advantage of the self-renewal and plasticity properties of stem cells, in this study, we successfully generated isogenic and six-cell clones of bone marrow-derived mesenchymal stem cells that carry the stop codon of the CCR5 gene by using a ZFN-mediated homology-directed repair technique. These cells were expandable for more than 5 passages, and thus show potential to serve as an individual’s cell factory. When Oct4 was overexpressed, the mutated cells robustly converted to CD34+ progenitor cells. Conclusion We here reported the novel approach on generation of patients own CD34 cells from high fidelity ZFN-mediated HDR MSC clones. We believe that our approach will be beneficial in future HIV treatment

NIH research grant to use ZFNs to treat Hepatitis B

Here is a copy of the abstract:

Anti-HBV therapeutics based on rare-cutting targeted endonucleases
   Fred Hutchinson Cancer Research Center, Seattle, WA, United States                


We propose to develop an alternative approach to address and treat HBV infection with targeted rare-cutting endonucleases. We will use zinc finger nucleases (ZFNs) to induce double-strand breaks within specific HBV sequences upon AAV-mediated ZFN delivery. We hope to achieve virologic cure of infected cells by promoting cellular degradation of cccDNA present in infected hepatocytes upon linearization or inactivating HBV genes within the episomal cccDNA. The repair mechanism for double-strand breaks is error prone and should result in disruption of genes around the cleaved target sequence. This proposal will study the efficacy and safety of our approach in the highly relevant humanized uPA-SCID mouse model of HBV infection. Our preliminary data shows that we can successfully mutate targeted HBV genes and inhibit HBV replication in an in vitro cell culture model of HBV using AAV-delivered ZFNs. It also shows that our HBV-specific ZFNs cause minimal levels of off-target cleavage at similar sites within the human genome. We have established the uPA-SCID mouse model of HBV infection and have demonstrated efficient delivery of a fluorescent reporter gene to human hepatocytes in humanized mouse livers using AAV vectors. Our comprehensive preliminary data provides the basis for a pilot study of the antiviral efficacy of this therapeutic approach in vivo. The overall aim of this study is to provide proof of principle fr its use in treating chronic HBV infections.

Public Health Relevance

The long-term goal of this project is to combine our team's unique expertise in rare cutting endonuclease technologies (ZFNs, TALENs and homing endonucleases), virology, gene delivery systems, and mouse models of HBV infection to generate a therapeutic approach allowing us to specifically target and disrupt hepatitis B virus genomes in livers of chronically infected individuals. This plan offers a plausible way to test the proof of principle for this therapy with the long-term aim of providing a cure for individuals infected with HBV.